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East Asian Arch Psychiatry 2025;35:11-5 | https://doi.org/10.12809/eaap2455

ORIGINAL ARTICLE

Effect of Ajwa dates on quality of life and serum tumour necrosis factor-alpha levels in patients with schizophrenia treated with risperidone: a randomised controlled study

Rismayanti, Limoa Erlyn, Syamsuddin Saidah, Seweng Arifin, Andi Mappaware Nasrudin, Renaldi Rinvil, Lisal Sonny Teddy

Full Paper in PDF

Abstract

Objectives: This study aimed to investigate the adjuvant treatment effect of Ajwa dates (Phoenix dactylifera L) on quality of life (QoL) and serum tumour necrosis factor-alpha (TNF-α) levels in patients with schizophrenia treated with risperidone.

Methods: Consecutive hospitalised patients aged 20 to 45 years who were diagnosed with schizophrenia, treated with risperidone at 4 to 6 mg/day, with a disease onset of ≤5 years, and had passed the acute phase were invited to participate. Participants were randomly and equally assigned to either the treatment or control group. The treatment group received risperidone as prescribed and seven Ajwa dates per day (ie, 60-80 g), whereas the control group received risperidone alone. Patient QoL was assessed by a psychiatrist in face-to-face interviews using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) at baseline, week 4, and week 8. Serum TNF-α levels were assessed using the enzyme-linked immunosorbent assay at baseline and week 8.

Results: In total, 44 participants were included in the analysis. The treatment and control groups were comparable in terms of baseline characteristics, except for education level (p = 0.037) and WHOQOL- BREF physical domain score (p = 0.002). At week 8, compared with the control group, the treatment group had higher total WHOQOL-BREF scores (69.3 vs 66.8, p = 0.015) and a greater percentage increase in scores (283.6% vs 243.4%), as well as lower TNF-α levels (86.8 vs 134.5 pg/mL, p = 0.046) and a greater percentage decrease in levels (-25.5% vs -8.6%). The WHOQOL-BREF scores were negatively correlated with serum TNF-α levels in both the treatment (r = -0.988, p < 0.001) and control (r = -0.918, p < 0.001) groups.

Conclusion: Ajwa dates have an adjuvant effect on improving QoL and reducing serum TNF-α levels in patients with schizophrenia treated with risperidone.

Key words: Quality of life; Risperidone; Schizophrenia; Tumor necrosis factor-alpha

Rismayanti, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
Limoa Erlyn, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
Syamsuddin Saidah, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
Seweng Arifin, Department of Biostatistics, Faculty of Public Health, Hasanuddin University, Makassar, South Sulawesi, Indonesia
Andi Mappaware Nasrudin, Department of Obstetrics and Gynaecology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
Renaldi Rinvil, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
Lisal Sonny Teddy, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia

Address for correspondence: Dr Limoa Erlyn, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10 Tamalanrea, Makassar, South Sulawesi, 90245, Indonesia. Email: erlynliem17@gmail.com

Submitted: 24 October 2024; Accepted: 6 January 2025

Introduction

Mental disorders are associated with disability, reduced productivity, and significant treatment costs.1,2 They often begin with a psychopathological phase that is mild, pervasive, and easily transitioned to the next stage.3 Schizophrenia is a serious mental disorder affecting 1% of the population worldwide.4 More than 21 million people with schizophrenia are at high risk of dying at a young age.1

Schizophrenia is characterised by cognitive decline, hallucinations, delusions, disorganised thinking, social withdrawal,5-7 and a reduced ability to interact socially.8 These symptoms affect personal, social, and occupational functioning,9 leading to reduced life expectancy by approximately 15 years.10 According to the American Psychiatric Association, social dysfunction is a main criterion for schizophrenia and affects interpersonal relationships, work, and/or self-care.11 Medications for schizophrenia largely focus on specific neurotransmitters, although multi-neurotransmitter psychopathology is increasingly recognised.12 Risperidone is effective in managing positive and negative symptoms but is often inadequate in addressing functional and social impairment.13,14

People with schizophrenia face significant clinical and psychosocial challenges and have a lower quality of life (QoL).15-17 The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) covers physical health, psychological wellbeing, social relationships, and relationships with one’s environment; it is commonly used to assess QoL.18,19

High levels of inflammatory markers such as tumour necrosis factor-alpha (TNF-α) may predict disease progression and response to treatment in schizophrenia.20 TNF-α is involved in neuroimmune regulation and autoimmunity, regulation of neuronal development, repair of neuronal damage, feedback signalling, differentiation of glial cells during early growth, and maintenance of normal brain morphology.21 Risperidone is not fully effective in addressing the functional and social impairments associated with schizophrenia.13,14 Therefore, a more effective and holistic therapeutic approach is needed.

The metabolite profiles of dates include all metabolites of amino acids, sugars, organic acids, phenolates, flavonoids, antioxidants, and macrominerals.22 Ajwa date fruit (Phoenix dactylifera L) contains various bioactive substances, such as phenolics and flavonoids, which have anti-inflammatory and antioxidant properties that can reduce oxidative stress and inflammation, potentially contributing to neuroprotection and improved immune regulation.23-25 This study aimed to investigate the adjuvant treatment effect of Ajwa dates on QoL and serum TNF-α levels in patients with schizophrenia treated with risperidone.

Methods

This randomised controlled trial was conducted between May 2023 and March 2024 (fasting periods during Ramadan were not included) at the Dadi Makassar Regional Mental Hospital, South Sulawesi, Indonesia. Consecutive hospitalised patients aged 20 to 45 years who were diagnosed with schizophrenia (based on ICD-10 criteria), treated with risperidone at 4 to 6 mg/day, with a disease onset of ≤5 years, and had passed the acute phase (with a score of <15 in the Positive and Negative Syndrome Scale– Excited Component) were invited to participate. Patients with physical comorbidities, a history of drug use, or treatment with anti-inflammatory, antioxidant, or antibiotic drugs were excluded.

Participants were randomly and equally assigned to either the treatment or control group. The treatment group received risperidone as prescribed and seven Ajwa dates per day (ie, 60-80 g), whereas the control group received risperidone alone. Patient QoL was assessed by a psychiatrist in face-to-face interviews using the WHOQOL-BREF at baseline, week 4, and week 8. Serum TNF-α levels were assessed using the enzyme-linked immunosorbent assay at baseline and week 8.

Statistical analyses were performed using SPSS (Windows version 24.0; IBM Corp, Armonk [NY], United States). The two groups were compared using the Chi- squared test, independent t test, or Mann-Whitney U test. Correlation between QoL and serum TNF-α levels was assessed using the Spearman correlation analysis. A p value of <0.05 was considered statistically significant.

Results

In total, 44 participants were included in the analysis. The treatment and control groups were comparable in terms of baseline characteristics, except for education level (p = 0.037, Table 1) and WHOQOL-BREF physical domain score (p = 0.002, Table 2). At week 8, compared with the control group, the treatment group had higher total WHOQOL-BREF scores (69.3 vs 66.8, p = 0.015) and a greater percentage increase in scores (283.6% vs 243.4%), as well as lower TNF-α levels (86.8 vs 134.5 pg/mL, p = 0.046, Table 3) and a greater percentage decrease in levels (-25.5% vs -8.6%). The WHOQOL-BREF scores were negatively correlated with serum TNF-α levels in both the treatment (r = -0.988, p < 0.001) and control (r = -0.918, p < 0.001) groups (Figure).

Discussion

The efficacy of risperidone in patients with schizophrenia is well documented.26-29 Nonetheless, supplementation with Ajwa dates resulted in better improvements in QoL and serum TNF-α levels in patients with schizophrenia treated with risperidone. Reduction of TNF-α levels may be associated with improvement of QoL in patients with schizophrenia. Ajwa dates contain rich nutrients and bioactive components, particularly anti-inflammatory compounds such as polyphenolic substances (ie, flavonoids, glycosides, and phenolics), which may improve symptoms in polyphenolic substances, particularly flavonoids, and may help suppress inflammatory effects.

11 T1

11 T2

11 T3

Quercetin, a member of the flavonol subfamily, has a potential role in the treatment of various central nervous system disorders.33 Consumption of foods rich in flavonoids significantly improves cognitive abilities and prevents or delays the development of related neurodegenerative disorders. Therefore, the therapeutic value of natural products can be attributed to their various neuropharmacological modulatory properties.34

The dosage of seven dates per day was in line with previous studies.35,36 A meta-analysis of studies of prenatal issues showed that the number of dates required to achieve optimal effect is at least six.37 Eating seven dates per day is not contraindicated with any medication. Furthermore, eating seven dates in the morning has a spiritual context for Muslims; Prophet Muhammad said “whoever eats seven Ajwa dates in the morning will not be harmed by poison or magic on that day”.

11 F1

This study has several limitations. The sample size was small due to difficulties in recruiting patients with schizophrenia. It used an open-label design, which may have led to potential biases. There was no placebo- controlled group. The effect of Ajwa dates on schizophrenia may have been direct or indirect (ie, by enhancing the effect of risperidone). Patients were recruited from a single hospital, and therefore the results of this study may not be generalisable to patients with other sociodemographic backgrounds or patients treated at other hospitals in Indonesia.

Conclusion

Ajwa dates have an adjuvant effect on improving QoL and reducing serum TNF-α levels in patients with schizophrenia treated with risperidone.

Contributors

All authors designed the study, acquired the data, analysed the data, drafted the manuscript, and critically revised the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

Conflicts of interest

All authors have disclosed no conflicts of interest.

Funding / support

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

All data generated or analysed during the present study are available from the corresponding author on reasonable request.

Ethics approval

This study was approved by the Biomedical Research Ethics Committee on Humans, Faculty of Medicine, Hasanuddin University (reference: 688/UN4.6.4.5.31/ PP36/ 2023). This study was registered in the Thai Clinical Trials Registry (reference: TCTR20241117003). The participants provided written informed consent for all treatments and procedures and for publication.

Acknowledgement

We thank Dr Andi Agus Mumang for providing suggestions to improve the manuscript.

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